A: Transfer a volume of Oral Suspension,equivalent to about 200mg of ibuprofen,to a separator containing about 10mLof chloroform,and shake for about 1minute.Allow the layers to separate,and pass the lower chloroform layer through a filter containing about 2g of anhydrous sodium sulfate.Use the filtrate as the test solution.[NOTE—Retain a portion of this test solution for use in Identification test B.]Separately apply 10-µLportions of the test solution and of a Standard solution containing 20mg per mLof USP Ibuprofen RSin chloroform to a thin-layer chromatographic plate (see Chromatography á621ñ)coated with a 0.25-mm layer of chromatographic silica gel and previously activated by heating at 105for 30minutes.Allow the spots to dry,and develop the chromatogram in a solvent system consisting of a mixture of n-hexane,butyl acetate,and glacial acetic acid (17:3:1)until the solvent front has moved about three-fourths of the length of the plate.Remove the plate from the chamber,mark the solvent front,and dry in a current of cool air.Examine the chromatograms under short-wavelength UVlight:the RFvalue of the principal spot obtained from the test solution corresponds to that obtained from the Standard solution.

B: Infrared Absorption á197Kñ—Prepare the test specimen and the standard as follows.Evaporate about 20drops of the test solution and the Standard solution retained from Identificationtest Ato dryness in a current of air without heating.

Medium: pH7.2phosphate buffer (see Buffer Solutionsin the section Reagents,Indicators,and Solutions);900mL.

Apparatus 2: 50rpm.

Time: 60minutes.

Mobile phaseand Chromatographic system— Proceed as directed in the Assay.

Internal standard solution— Prepare a solution of benzophenone in acetonitrile containing about 0.3mg per mL.

Standard solution— Dissolve an accurately weighed quantity of USP Ibuprofen RSin Dissolution Mediumto obtain a solution having a known concentration of about 0.011Jmg per mL,Jbeing the labeled quantity,in mg,of ibuprofen in each mLof the Oral Suspension.Mix 10.0mLof this solution and 10.0mLof the Internal standard solution,pass the mixture through a filter having a 0.5-µm or finer porosity,and use the filtrate as the Standard solution.

Test solution— Filter a portion of the solution under test.Mix 10.0mLof the filtrate and 10.0mLof the Internal standard solution,pass the mixture through a filter having a 0.5-µm or finer porosity,and use the filtrate as the Test solution.

Procedure— Using an accurately tared syringe,draw about 10mLof well-mixed Oral Suspension into the syringe,which is connected to tubing,and accurately weigh.[NOTE—The tubing of the syringe is placed into a zone that is between the surface of the Dissolution Medium and the top of the rotating blade.]Express the Oral Suspension into the Dissolution Medium.Promptly reweigh the syringe,and determine the weight,WU,in g,of the Oral Suspension added to the Dissolution Medium.Separately inject equal volumes (about 10µL)of the Standard solutionand the Test solutioninto the chromatograph,record the chromatograms,and measure the areas for the major peaks.Calculate the percentage of the labeled amount of C13H18O2dissolved by the formula: in which Cis the concentration,in mg per mL,of USP Ibuprofen RSin the Standard solution;Lis the labeled quantity,in mg per mL,of ibuprofen in the Oral Suspension;Dis the density,in g per mL,of the Oral Suspension,determined as directed for Densityin the Assay;WUis the weight,in g,of the Oral Suspension added to the Dissolution Medium;and RUand RSare the ratios of the ibuprofen peak areas to the benzophenone peak areas obtained from the Test solutionand the Standard solution,respectively.

Tolerances— Not less than 80%(Q)of the labeled amount of C13H18O2is dissolved in 60minutes.

Add the following:

FOR ORAL SUSPENSION PACKAGED IN SINGLE-UNIT CONTAINERS: meets the requirements.USP28

Change to read:

FOR ORAL SUSPENSION PACKAGED IN MULTIPLE-UNIT CONTAINERS: meets the requirements.USP28

Mobile phaseand Diluent— Proceed as directed in the Assay.

Standard solution— Quantitatively dissolve an accurately weighed quantity of 4-isobutylacetophenone in acetonitrile to obtain a stock solution having a known concentration of about 0.5mg per mL.Transfer 3.0mLof this stock solution to a 50-mLvolumetric flask,dilute with Diluentto volume,and mix.Transfer 2.0mLof this solution to a second 50-mLvolumetric flask,add 18mLof Diluent,dilute with acetonitrile to volume,mix,and pass through a filter having a porosity of 0.22µm.This Standard solutioncontains about 0.0012mg of 4-isobutylacetophenone per mL.

Test solution— Transfer 20.0mLof the portion of the stock solution retained from the Assay preparationin the Assayinto a 50-mLvolumetric flask,dilute with acetonitrile to volume,mix,and pass through a filter having a 0.22-µm porosity.

System suitability solution— Transfer 1.5mLof the stock solution of 4-isobutylacetophenone prepared as directed for Standard solutionand 9mLof the stock solution of USP Ibuprofen RSprepared as directed for Standard preparationin the Assayto a 25-mLvolumetric flask,dilute with acetonitrile to volume,mix,and pass through a filter having a 0.22-µm porosity.This solution contains about 0.03mg of 4-isobutylacetophenone and about 0.4mg of USP Ibuprofen RSper mL.

Chromatographic system(see Chromatography á621ñ)— The liquid chromatograph is equipped with a 254-nm detector and a 4.6-mm ×15-cm column that contains 5-µm packing L7.The flow rate is about 2mLper minute.Chromatograph the System suitability solution,and record the peak responses as directed for Procedure:the relative retention times are about 1.3for 4-isobutylacetophenone and 1.0for ibuprofen;the tailing factor is not more than 2.0;and the resolution,R,between ibuprofen and 4-isobutylacetophenone is not less than 1.5.Chromatograph the Standard solution,and record the peak responses as directed for Procedure:the relative standard deviation for replicate injections is not more than 2.0%.

Procedure— Separately inject equal volumes (about 35µL)of the Standard solutionand the Test solutioninto the chromatograph,record the chromatograms,and measure the areas for the major peaks.Calculate the percentage of 4-isobutylacetophenone in the Oral Suspension,based on the labeled content of ibuprofen,taken by the formula: in which Cis the concentration,in mg per mL,of 4-isobutylacetophenone in the Standard solution;Dis the quantity,in mL,of Oral Suspension taken to prepare the stock solution for the Assay preparation;Lis the labeled quantity,in mg,of ibuprofen in each mLof Oral Suspension;and rUand rSare the 4-isobutylacetophenone peak areas obtained from the Test solutionand the Standard solution,respectively.Not more than 0.25%is found.

Mobile phase— Dilute 0.7mLof phosphoric acid with water to obtain 1000mLof 0.01Mphosphoric acid.Prepare a mixture of this solution and acetonitrile (63:37).Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).

Diluent— Prepare a mixture of acetonitrile and water (1:1).

Internal standard solution— Prepare a solution of benzophenone in acetonitrile containing about 3.2mg per mL.

Standard preparation— Quantitatively dissolve an accurately weighed quantity of USP Ibuprofen RSin Diluentto obtain a stock solution having a known concentration of about 1.2mg per mL.Transfer 20.0mLof this stock solution and 5.0mLof Internal standard solutionto a 50-mLvolumetric flask,dilute with acetonitrile to volume,mix,and filter.This solution contains about 0.48mg of USP Ibuprofen RSper mL.

Density— Using a tared 50-mLvolumetric flask,weigh 50mLof Oral Suspension that has been previously well shaken to ensure homogeneity,allow to stand until the entrapped air has risen,and finally invert carefully just prior to transferring it to the volumetric flask.From the observed weight of 50mLof the Oral Suspension,calculate the density,in g per mL,of the Oral Suspension.

Assay preparation— Transfer an accurately weighed portion of Oral Suspension,equivalent to about 60mg of Ibuprofen,to a 50-mLvolumetric flask,dilute with Diluentto volume,and mix (stock solution).Transfer 20.0mLof this stock solution and 5.0mLof Internal standard solutionto a second 50-mLvolumetric flask,dilute with acetonitrile to volume,mix,and filter.[NOTE—Retain a portion of the stock solution for use in the test for Limit of 4-isobutylacetophenone.]

Chromatographic system(see Chromatography á621ñ)— The liquid chromatograph is equipped with a 220-nm detector and a 4.6-mm ×15-cm column that contains 5-µm packing L7.The flow rate is about 2mLper minute.Chromatograph the Standard preparation,and record the peak responses as directed for Procedure:the relative retention times are about 0.9for benzophenone and 1.0for ibuprofen;the resolution,R,between benzophenone and ibuprofen is not less than 1.5;the tailing factor is not more than 2.0;and the relative standard deviation for replicate injections is not more than 2.0%.

Procedure— Separately inject equal volumes (about 5µL)of the Standard preparationand the Assay preparationinto the chromatograph,record the chromatograms,and measure the areas for the major peaks.Calculate the quantity,in mg,of C32H18O2in each mLof the Oral Suspension taken by the formula: in which Cis the concentration,in mg per mL,of USP Ibuprofen RSin the Standard preparation;Dis the density,in g per mL,of Oral Suspension;WUis the weight,in g,of the portion of Oral Suspension taken to prepare the Assay preparation;and RUand RSare the ratios of the ibuprofen peak areas to the benzophenone peak areas obtained from the Assay preparationand the Standard preparation,respectively.